TRIM21 is a novel regulator of Par-4 in colon and pancreatic cancer cells

Jeffrey Q. Nguyen, Rosalyn B. Irby

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

The prostate apoptosis response protein 4 (Par-4) is a tumor-suppressor that has been shown to induce cancer-cell selective apoptosis in a variety of cancers. The regulation of Par-4 expression and activity is a relatively understudied area, and identifying novel regulators of Par-4 may serve as novel therapeutic targets. To identify novel regulators of Par-4, a co-immunoprecipitation was performed in colon cancer cells, and co-precipitated proteins were identified by mass-spectometry. TRIM21 was identified as a novel interacting partner of Par-4, and further shown to interact with Par-4 endogenously and through its PRY-SPRY domain. Additional studies show that TRIM21 downregulates Par-4 levels in response to cisplatin, and that TRIM21 can increase the resistance of colon cancer cells to cisplatin. Furthermore, forced Par-4 expression can sensitize pancreatic cancer cells to cisplatin. Finally, we demonstrate that TRIM21 expression predicts survival in pancreatic cancer patients. Our work highlights a novel mechanism of Par-4 regulation, and identifies a novel prognostic marker and potential therapeutic target for pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)16-25
Number of pages10
JournalCancer Biology and Therapy
Volume18
Issue number1
DOIs
StatePublished - Jan 2 2017

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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